Tag Archives: lymph nodes

Calligraphy ink and cancer treatment

Courtesy of ACS Omega and the researchers

Nice illustration! I wish I could credit the artist. For anyone who needs a little text to make sense of it, there’s a Sept. 27, 2017 news item on Nanowerk (Note: A link has been removed),

For hundreds of years, Chinese calligraphers have used a plant-based ink to create beautiful messages and art. Now, one group reports in ACS Omega (“New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes”) that this ink could noninvasively and effectively treat cancer cells that spread, or metastasize, to lymph nodes.

A Sept. 27, 2017 American Chemical Society (ACS) news release, which originated the news item, reveals more about the research,

As cancer cells leave a tumor, they frequently make their way to lymph nodes, which are part of the immune system. In this case, the main treatment option is surgery, but this can result in complications. Photothermal therapy (PTT) is an emerging noninvasive treatment option in which nanomaterials are injected and accumulate in cancer cells. A laser heats up the nanomaterials, and this heat kills the cells. Many of these nanomaterials are expensive, difficult-to-make and toxic. However, a traditional Chinese ink called Hu-Kaiwen ink (Hu-ink) has similar properties to the nanomaterials used in PTT. For example, they are the same color, and are both carbon-based and stable in water. So Wuli Yang and colleagues wanted to see if Hu-ink could be a good alternative material for PTT.

The researchers analyzed Hu-ink and found that it consists of nanoparticles and thin layers of carbon. When Hu-ink was heated with a laser, its temperature rose by 131 degrees Fahrenheit, much higher than current nanomaterials. Under PPT conditions, the Hu-ink killed cancer cells in a laboratory dish, but under normal conditions, the ink was non-toxic. This was also the scenario observed in mice with tumors. The researchers also noted that Hu-ink could act as a probe to locate tumors and metastases because it absorbs near-infrared light, which goes through skin.

Being a little curious about Hu-ink’s similarity to nanomaterial, I looked for more detail in the the paper (Note: Links have been removed), From the: Introduction,

Photothermal therapy (PTT) is an emerging tumor treatment strategy, which utilizes hyperthermia generated from absorbed near-infrared (NIR) light energy by photoabsorbing agents to kill tumor cells.(7-13) Different from chemotherapy, surgical treatment, and radiotherapy, PTT is noninvasive and more efficient.(7, 14, 15) In the past decade, PTT with diverse nanomaterials to eliminate cancer metastases lymph nodes has attracted extensive attention by several groups, including our group.(3, 16-20) For instance, Liu and his co-workers developed a treatment method based on PEGylated single-walled carbon nanotubes for PTT of tumor sentinel lymph nodes and achieved remarkably improved treatment effect in an animal tumor model.(21) To meet the clinical practice, the potential metastasis of deeper lymph nodes was further ablated in our previous work, using magnetic graphene oxide as a theranostic agent.(22) However, preparation of these artificial nanomaterials usually requires high cost, complicated synthetic process, and unavoidably toxic catalyst or chemicals,(23, 24) which impede their future clinical application. For the clinical application, exploring an environment-friendly material with simple preparation procedure, good biocompatibility, and excellent therapeutic efficiency is still highly desired. [emphases mine]

From the: Preparation and Characterization of Hu-Ink

To obtain an applicable sample, the condensed Hu-ink was first diluted into aqueous dispersion with a lower concentration. The obtained Hu-ink dispersion without any further treatment was black in color and stable in physiological environment, including water, phosphate-buffered saline (PBS), and Roswell Park Memorial Institute (RPMI) 1640; furthermore, no aggregation was observed even after keeping undisturbed for 3 days (Figure 2a). The nanoscaled morphology of Hu-ink was examined by transmission electron microscopy (TEM) (Figure 2b), which demonstrates that Hu-ink mainly exist in the form of small aggregates. These small aggregates consist of a few nanoparticles with diameter of about 20–50 nm. Dynamic light scattering (DLS) measurement (Figure 2c) further shows that Hu-ink aqueous dispersion possesses a hydrodynamic diameter of about 186 nm (polydispersity index: 0.18), which was a crucial prerequisite for biomedical applications.(29) In the X-ray diffraction (XRD) pattern, no other characteristic peaks are found except carbon peak (Figure S1, Supporting Information), which confirms that the main component of Hu-ink is carbon.(25) Raman spectroscopy was a common tool to characterize graphene-related materials.(30) D band (∼1300 cm–1, corresponding to the defects) and G band (∼1600 cm–1, related to the sp2 carbon sites) peaks could be observed in Figure 2d with the ratio ID/IG = 0.96, which confirms the existence of graphene sheetlike structure in Hu-ink.(31) The UV–vis–NIR spectra (Figure 2e) also revealed that Hu-ink has high absorption in the NIR region around 650–900 nm, in which hemoglobin and water, the major absorbers of biological tissue, have their lowest absorption coefficient.(32) The high NIR absorption capability of Hu-ink encouraged us to investigate its photothermal properties.(33-35) Hu-ink dispersions with different concentrations were irradiated under an 808 nm laser (the commercial and widely used wavelength in photothermal therapy).(8-13) [emphases mine]

Curiosity satisfied! For those who’d like to investigate even further, here’s a link to and a citation for the paper,

New Application of Old Material: Chinese Traditional Ink for Photothermal Therapy of Metastatic Lymph Nodes by Sheng Wang, Yongbin Cao, Qin Zhang, Haibao Peng, Lei Liang, Qingguo Li, Shun Shen, Aimaier Tuerdi, Ye Xu, Sanjun Cai, and Wuli Yang. ACS Omega, 2017, 2 (8), pp 5170–5178 DOI: 10.1021/acsomega.7b00993 Publication Date (Web): August 30, 2017

Copyright © 2017 American Chemical Society

This paper appears to be open access.

Nanoparticles from tattoo inks circulate through your body

English: Tattoo of Hand of Fatima,. Model: Casini. Date: 4 July 2017, 18:13:41. Source : Own work. Author: Stephencdickson.

For those who like their news in video format, there’s this Canadian Broadcasting Corporation (CBC) news item broadcast on Sep. 11, 2017 (after the commercials),

For those who like text and more detail, scientists at the European Synchrotron Radiation Facility (ESRF) have produced a study of the (at the nanoparticle scale) inks in tattoos. From a Sept. 12, 2017 news item on phys.org,

The elements that make up the ink in tattoos travel inside the body in micro and nanoparticle forms and reach the lymph nodes, according to a study published in Scientific Reports on 12 September [2017] by scientists from Germany and the ESRF, the European Synchrotron, Grenoble (France). It is the first time researchers have found analytical evidence of the transport of organic and inorganic pigments and toxic element impurities as well as in depth characterization of the pigments ex vivo in tattooed tissues. Two ESRF beamlines were crucial in this breakthrough.

A Sept. 12, 2017 ESRF press release (also on EurkeAlert), which originated the news item, explains further,

The reality is that little is known about the potential impurities in the colour mixture applied to the skin. Most tattoo inks contain organic pigments, but also include preservatives and contaminants like nickel, chromium, manganese or cobalt. Besides carbon black, the second most common ingredient used in tattoo inks is titanium dioxide (TiO2), a white pigment usually applied to create certain shades when mixed with colorants. Delayed healing, along with skin elevation and itching, are often associated with white tattoos, and by consequence with the use of TiO2. TiO2 is also commonly used in food additives, sun screens and paints. Scientists from the ESRF, the German Federal Institute for Risk Assessment, Ludwig-Maximilians University, and the Physikalisch-Technische Bundesanstalt have managed to get a very clear picture on the location of titanium dioxide once it gets in the tissue. This work was done on the ESRF beamlines ID21 and ID16B.

drawing tattookinetics.jpg

Translocation of tattoo particles from skin to lymph nodes. Upon injection of tattoo inks, particles can be either passively transported via blood and lymph fluids or phagocytized by immune cells and subsequently deposited in regional lymph nodes. After healing, particles are present in the dermis and in the sinusoids of the draining lymph nodes. Credits: C. Seim.

The hazards that potentially derive from tattoos were, until now, only investigated by chemical analysis of the inks and their degradation products in vitro. “We already knew that pigments from tattoos would travel to the lymph nodes because of visual evidence: the lymph nodes become tinted with the colour of the tattoo. It is the response of the body to clean the site of entrance of the tattoo. What we didn’t know is that they do it in a nano form, which implies that they may not have the same behaviour as the particles at a micro level. And that is the problem: we don’t know how nanoparticles react”, explains Bernhard Hesse, one of the two first authors of the study (together with Ines Schreiver, from the German Federal Institute for Risk Assessment) and ESRF visiting scientist.


Particle mapping and size distribution of different tattoo pigment elements.  a, d) Ti and the Br containing pigment phthalocyanine green 36 are located next to each other. b, e) Log scale mappings of Ti, Br and Fe in the same areas as displayed in a) and d) reveal primary particle sizes of different pigment species. c, f) Magnifications of the indicated areas in b) and e), respectively. Credits: C. Seim.

X-ray fluorescence measurements on ID21 allowed the team to locate titanium dioxide at the micro and nano range in the skin and the lymphatic environment. They found a broad range of particles with up to several micrometres in size in human skin, but only smaller (nano) particles transported to the lymph nodes. This can lead to the chronic enlargement of the lymph nodes and lifelong exposure. Scientists also used the technique of Fourier transform infrared spectroscopy to assess biomolecular changes in the tissues in the proximity of the tattoo particles.


Ines Schreiver doing experiments on ID16B with Julie Villanova. Credits: B. Hesse.

Altogether the scientists report strong evidence for both migration and long-term deposition of toxic elements and tattoo pigments as well as for conformational alterations of biomolecules that are sometimes linked to cutaneous adversities upon tattooing.

Then next step for the team is to inspect further samples of patients with adverse effects in their tattoos in order to find links with chemical and structural properties of the pigments used to create these tattoos.

Here’s a link to and  a citation for the paper,

Synchrotron-based ν-XRF mapping and μ-FTIR microscopy enable to look into the fate and effects of tattoo pigments in human skin by Ines Schreiver, Bernhard Hesse, Christian Seim, Hiram Castillo-Michel, Julie Villanova, Peter Laux, Nadine Dreiack, Randolf Penning, Remi Tucoulou, Marine Cotte, & Andreas Luch. Scientific Reports 7, Article number: 11395 (2017) doi:10.1038/s41598-017-11721-z Published online: 12 September 2017

This paper is open access.